Optimised pharmacokinetic and pharmacodynamic profiles in cardiovascular disease therapy

Desirable pharmacokinetic effects for β-blockers and calcium antagonists. Desirable pharmacokinetic properties of β-blockers and calcium antagonists include predictable absorption leading to a gradual onset of action and sustained presence of the drug and its effect over a 24-h dosing interval. The former can be achieved either pharmaceutically by a controlled-release drug formulation or pharmacodynamically with a slow onset of action due to the physiological characteristics of the drug target. The latter is achieved either by developing drug molecules with a low intrinsic clearance or, again, pharmaceutically by controlling the rate of drug input with a controlled-release drug formulation. Both of these approaches to β-adrenoceptor blockers and calcium antagonists have been effectively exploited to improve the therapy of hypertension. The clinical pharmacodynamic profile should include substantial and sustained antihypertensive or anti-anginal effects over a 24-h period. New calcium antagonists. In the case of calcium antagonists, efforts to achieve an optimal profile have been primarily pharmacokinetic until recently, with the development of increasingly complex sustained-release formulations and efforts to develop low-clearance drugs. More recently, extension of the pharmacodynamic target with blockade of T-type calcium channels has been explored in an attempt to further optimize the clinical pharmacodynamic profile of this drug class.